Romana Zaoralová

Gain(1)(q21) is an Unfavorable Genetic Prognostic Factor for Patients With Relapsed Multiple Myeloma Treated With Thalidomide but Not for Those Treated With Bortezomib

UNLABELLED Chromosomal aberrations are important prognostic factors in multiple myeloma diagnosis. We evaluated the effect common high-risk chromosomal aberrations in a cohort of 102 patients with relapsed disease treated with bortezomib or thalidomide. Our results showed that patients treated with thalidomide with a gain(1)(q21) had inferior survival compared with the bortezomib group. Therefore, bortezomib-based regiments are more effective for patients with relapsed multiple myeloma with an incidence of gain in the gain(1)(q21). BACKGROUND Prognostic impact of specific chromosomal aberrations in patients with relapsed multiple myeloma (MM) treated with the novel agents is briefly described. PATIENTS AND METHODS We analyzed the prognostic value of an extended panel of chromosomal aberrations [del(13)(q14), del(17)(p13), t(4;14)(p16;q32), gain(1)(q21), and hyperdiploidy] by using the technique of interphase fluorescence in situ hybridization in a cohort of 102 patients with relapsed MM treated with thalidomide- or bortezomib-based protocols. RESULTS The gain(1)(q21) had a negative impact on overall survival for patients with MM treated with thalidomide (15.7 vs. 41.3 months; P = .004). Moreover, we confirmed the negative impact of the cumulative effect of 2 or more cytogenetic changes that occur simultaneously on the overall survival in the thalidomide group (20.3 months vs. not yet reached; P = .039). We did not find any significant impact of the aberrations studied on overall survival in the bortezomib cohort of patients. CONCLUSION We conclude that bortezomib-based protocols are able to partially overcome the negative prognostic impact of the tested chromosomal abnormalities in patients with relapsed MM.

Centrosome amplification as a possible marker of mitotic disruptions and cellular carcinogenesis in multiple myeloma.

Centrosome amplification (CA) as a potential marker of mitotic disruptions in multiple myeloma (MM) was investigated in two populations of B-cell lineage: B-cells and plasma cells (PCs). Using immunofluorescent staining, it was shown that CA in B-cells is present in 3.2+/-2.5% in healthy donors versus 9.9+/-7.9% in MM patients (p<0.0001). Based on the calculated threshold value of CA in B-cells, 37% (14/38) of MM patients were positive. There was no significant correlation between CA-positive MM cases (based on PC samples evaluation) and the occurrence of cytogenetic abnormalities in PCs, including del(13)(q14), del(17)(p13), gain(1)(q21) and hyperdiploidy.